Infection of humans with Hepatitis B virus (HBV) results in a broad range of clinical symptoms, from mild, inapparent disease, fulminant hepatitis to hepatocellular carcinoma. Due to the lack of an in vitro infection system for HBV, early events of infectious processes are poorly understood. Our interest in this study is to investigate the regulatory functions of an HBV-encoded protein X (pX) in the infected hepatocytes, and to gain insight into the mechanisms of its action. Studies proposed here are aimed at exploring the participation of pX in gene expression and liver cell proliferation associated with viral infection. It will be important to define the exact mechanism of trans-activation by the X protein in order to understand how pX operates in conjunction with cellular proteins during the establishment and maintenance of viral infection in the hepatocyte. HBV pX was shown by this laboratory to function via protein-protein interactions. In this study our principal focus will be to identify liver cellular proteins from HBV-infected livers and liver tumors and attempt to characterize those interactions and their possible relevance to processes of liver disease pathogenesis.